The family Flaviviridae contains at least 70 arthropod-transmitted viruses, many of which infect humans and other vertebrates. A subgroup of the Flaviviridae family, the Japanese encephalitis serocomplex, includes West Nile Virus, St. Louis encephalitis, Murray Valley encephalitis and kunjin viruses. West Nile virus, in particular, is most commonly found in Africa and the Middle East.
All flaviviruses, including West Nile Virus, St Louis encephalitis, dengue, Japanese encephalitis, yellow fever and kunjin viruses share similar size, symmetry and appearance. Despite the fact that flaviviruses may use different process to enter a host cell, such as endocytotis (described for West Nile Virus and Kunjin Virus) and direct fusion of the cell (described for dengue and Encephalitis Virus), entry of all flaviviruses into the host-cell involves an interaction between the virus and a receptor of the cell.
Several studies have shown that the viral envelope protein of flaviviruses plays a crucial role in mediating virus-host cellular receptor interaction. Based on crystallography data of tick-borne encephalitis flavivirus viral envelope protein, Rey and colleagues (1995) noted that each viral envelope protein monomer is folded into 3 distinct domains. A central domain I is the antigenic domain that carries the N-glycosylation site. Domain II of the viral envelope protein is believed to be responsible for pH-dependent fusion of the viral envelope protein to the endosomal membrane during uncoating, and domain III is important for flavivirus binding to host cells.
With reference to West Nile virus, Beasley and Barrett (2002) focused on the importance of subportions of the Domain III in West Nile virology. They identified and mapped as epitopes, portions of Domain III whose neutralization by single monoclonal antibodies may result in neutralization of the virus.
The specific interaction between flaviviruses and a vertebrate cell surface or surface membrane receptor is unknown. Without knowledge of the details of this interaction, it has proven difficult to specifically treat or prevent the disease. Therefore, there is clearly a need for the identification of the cell receptor, as well as the domain/s of the flavivirus that mediate their respective interactions.